Using recently developed super-resolution microscopic techniques and a three-dimensional bioengineered model that mimics the connective tissue found in atherosclerotic plaques, researchers from HMS and Brigham and Women’s Hospital have followed the formation of cardiovascular microcalcifications in real time, providing key insights into blockages that can lead to heart failure. The team’s work could propel innovations in imaging technology that would help advance therapeutic interventions for heart patients. The results of the study were published online on January 11, 2016, in Nature Materials.
Coronary calcium scores can predict cardiovascular events in patients, but microcalcifications in the coronary arteries can be so small that traditional imaging techniques cannot detect them.
Using high-resolution imaging techniques, the research team, led by Elena Aikawa, an HMS associate professor of medicine at Brigham and Women’s, and Joshua Hutcheson, an HMS research fellow in medicine at the hospital, pinpointed extracellular vesicles that led to the formation of microcalcifications and observed their growth into stable, larger structures or, at vulnerable sites, cause plaque destabilization and rupture—a major cause of heart attacks.
“We can now use this system to visualize what is happening and explore how to intervene in this process,” says Aikawa, who also directs the Vascular Biology Program at Brigham and Women’s Center for Interdisciplinary Cardiovascular Sciences. “With the knowledge that we’ve gained here, we can pick out the key extracellular vesicles and find ways to target them before microcalcifications take shape.”
The structured illumination and other high-resolution microscopy techniques used in this research cannot currently be used in patients, but the researchers hope that innovations in imaging will help move this technology forward and that future studies of the proteins involved in plaque formation will help identify points of therapeutic intervention.
Image: Elena Aikawa group